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"Cytology"
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Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors
by
de Bruijn, Marella F.
,
Schulz, Christian
,
Trouillet, Celine
in
13/31
,
14/63
,
631/136/232/2059
2015
To determine the origin of adult tissue-resident macrophages, a mouse lineage tracing study has revealed that these cells derive from erythro-myeloid progenitors in the yolk sac that are distinct from fetal and adult haematopoietic stem cells.
The origin of adult myeloid cells
The developmental origin of tissue-resident macrophage progenitors and their contribution to macrophages in fetal and adult organs relative to bone marrow macrophages are still unclear. Using lineage tracing, Elisa Gomez Perdiguero
et al
. identify a population of yolk-sac-derived progenitors — distinct from fetal and adult haematopoetic stem cells — that gives rise to erythrocytes, macrophages, granulocytes and monocytes in the young mouse fetus, and to the vast majority of adult tissue-resident macrophages.
Most haematopoietic cells renew from adult haematopoietic stem cells (HSCs)
1
,
2
,
3
, however, macrophages in adult tissues can self-maintain independently of HSCs
4
,
5
,
6
,
7
. Progenitors with macrophage potential
in vitro
have been described in the yolk sac before emergence of HSCs
8
,
9
,
10
,
11
,
12
,
13
, and fetal macrophages
13
,
14
,
15
can develop independently of
Myb
4
, a transcription factor required for HSC
16
, and can persist in adult tissues
4
,
17
,
18
. Nevertheless, the origin of adult macrophages and the qualitative and quantitative contributions of HSC and putative non-HSC-derived progenitors are still unclear
19
. Here we show in mice that the vast majority of adult tissue-resident macrophages in liver (Kupffer cells), brain (microglia), epidermis (Langerhans cells) and lung (alveolar macrophages) originate from a
Tie2
+
(also known as
Tek
) cellular pathway generating
Csf1r
+
erythro-myeloid progenitors (EMPs) distinct from HSCs. EMPs develop in the yolk sac at embryonic day (E) 8.5, migrate and colonize the nascent fetal liver before E10.5, and give rise to fetal erythrocytes, macrophages, granulocytes and monocytes until at least E16.5. Subsequently, HSC-derived cells replace erythrocytes, granulocytes and monocytes. Kupffer cells, microglia and Langerhans cells are only marginally replaced in one-year-old mice, whereas alveolar macrophages may be progressively replaced in ageing mice. Our fate-mapping experiments identify, in the fetal liver, a sequence of yolk sac EMP-derived and HSC-derived haematopoiesis, and identify yolk sac EMPs as a common origin for tissue macrophages.
Journal Article
Human bone marrow harbors cells with neural crest-associated characteristics like human adipose and dermis tissues
by
Neirinckx, Virginie
,
Gothot, André
,
Coste, Cécile
in
Adipose tissue
,
Adipose Tissue - cytology
,
Adipose Tissue - metabolism
2017
Adult neural crest stem-derived cells (NCSC) are of extraordinary high plasticity and promising candidates for use in regenerative medicine. Several locations such as skin, adipose tissue, dental pulp or bone marrow have been described in rodent, as sources of NCSC. However, very little information is available concerning their correspondence in human tissues, and more precisely for human bone marrow. The main objective of this study was therefore to characterize NCSC from adult human bone marrow. In this purpose, we compared human bone marrow stromal cells to human adipose tissue and dermis, already described for containing NCSC. We performed comparative analyses in terms of gene and protein expression as well as functional characterizations. It appeared that human bone marrow, similarly to adipose tissue and dermis, contains NESTIN+ / SOX9+ / TWIST+ / SLUG+ / P75NTR+ / BRN3A+/ MSI1+/ SNAIL1+ cells and were able to differentiate into melanocytes, Schwann cells and neurons. Moreover, when injected into chicken embryos, all those cells were able to migrate and follow endogenous neural crest migration pathways. Altogether, the phenotypic characterization and migration abilities strongly suggest the presence of neural crest-derived cells in human adult bone marrow.
Journal Article
Reprogramming in vivo produces teratomas and iPS cells with totipotency features
2013
Reprogramming of adult cells to generate induced pluripotent stem cells (iPS cells) has opened new therapeutic opportunities; however, little is known about the possibility of
in vivo
reprogramming within tissues. Here we show that transitory induction of the four factors
Oct4, Sox2, Klf4
and
c-Myc
in mice results in teratomas emerging from multiple organs, implying that full reprogramming can occur
in vivo
. Analyses of the stomach, intestine, pancreas and kidney reveal groups of dedifferentiated cells that express the pluripotency marker NANOG, indicative of
in situ
reprogramming. By bone marrow transplantation, we demonstrate that haematopoietic cells can also be reprogrammed
in vivo
. Notably, reprogrammable mice present circulating iPS cells in the blood and, at the transcriptome level, these
in vivo
generated iPS cells are closer to embryonic stem cells (ES cells) than standard
in vitro
generated iPS cells. Moreover,
in vivo
iPS cells efficiently contribute to the trophectoderm lineage, suggesting that they achieve a more plastic or primitive state than ES cells. Finally, intraperitoneal injection of
in vivo
iPS cells generates embryo-like structures that express embryonic and extraembryonic markers. We conclude that reprogramming
in vivo
is feasible and confers totipotency features absent in standard iPS or ES cells. These discoveries could be relevant for future applications of reprogramming in regenerative medicine.
Induced pluripotent stem cells (iPS cells) have been created
in vivo
by reprogramming mouse somatic cells with
Oct4
,
Sox2
,
Klf4
and
c-Myc
; these cells have totipotent features that are missing from
in vitro
created iPS cells or embryonic stem cells.
In vivo
production of iPS cells
Manuel Serrano and colleagues show for the first time that reprogramming of somatic cells to pluripotency by the classic 'Yamanaka factors' Oct4, Sox2, Klf4 and c-Myc can be achieved
in vivo
. Analysis of induced pluripotent stem (iPS) cells induced
in vivo
from stomach, intestine, pancreas and kidney cells in mice shows that they are closer to embryonic stem cells than
in vitro
-generated iPS cells. The
in vivo
iPS cells also have the potential to generate embryo-like structures that express embryonic and extraembryonic markers, which suggests that they have totipotent features not found in conventional iPS or embryonic stem cells.
Journal Article
What is cell theory?
Learn about cell theory, what it is, what it states, and the sequence of historical events that led to its development.
Combinatory differentiation of human induced pluripotent stem cells generates functional thymic epithelium driving dendritic cell and CD4/CD8 T cell development
2026
The thymus educates thymocytes through a selection process mediated by thymic epithelial cells (TECs). Recent advances have made the generation of T lymphocytes from induced pluripotent stem cells (iPSc) a promising therapeutic strategy. However, current approaches often fail to replicate the thymic niche, leading to impaired T cell generation. Here we address the production of functional mature iPSc-derived TECs supporting in vitro T cell generation. We optimize thymic lineage differentiation through an unbiased multifactorial experimental design. By modulating specific signaling pathways, we generate progenitors that mature into medullary and cortical TECs. Co-culture with primary hematopoietic progenitors in a 3D thymic organoid setup induces their differentiation into CD4
+
and CD8
+
T cells. Importantly, thymic organoids support multilineage differentiation, with dendritic cell populations also emerging. Thus, the presented thymic organoid model provides a practical platform for studying thymic cellular interactions and thymopoiesis in vitro, and opens further research perspectives towards cell-based therapies.
In vitro methods for thymic organoid cultures are useful to examine requirements for T cell development and for generating large numbers of cells for therapeutic purposes. Here the authors use human induced pluripotent stem cells, differentiate these into thymic epithelial organoid cultures and utilise haematopoietic progenitors to show development of T cells in vitro.
Journal Article
Cells
\"Follows the function of cells, how they're made, and the English scientist, Robert Hooke, who discovered them by examining a piece of cork.\"-- Publisher's website.
Schwann cell precursors contribute to skeletal formation during embryonic development in mice and zebrafish
by
Adameyko, Igor
,
Dyachuk, Vyacheslav
,
Kamenev, Dmitrii
in
Animal models
,
Animals
,
Biocompatibility
2019
Immature multipotent embryonic peripheral glial cells, the Schwann cell precursors (SCPs), differentiate into melanocytes, parasympathetic neurons, chromaffin cells, and dental mesenchymal populations. Here, genetic lineage tracing revealed that, during murine embryonic development, some SCPs detach from nerve fibers to become mesenchymal cells, which differentiate further into chondrocytes and mature osteocytes. This occurred only during embryonic development, producing numerous craniofacial and trunk skeletal elements, without contributing to development of the appendicular skeleton. Formation of chondrocytes from SCPs also occurred in zebrafish, indicating evolutionary conservation. Our findings reveal multipotency of SCPs, providing a developmental link between the nervous system and skeleton.
Journal Article